Dr. Rajeev Venkayya is a postdoctoral fellow in the Lung Biology Center at UCSF/San Francisco General Hospital. He has completed 20 months of training in the Cardiovascular Research Institute training program, and is committed to pursuing a career in research. To this end, he has participated in a comprehensive training program that will continue during the tenure of the MCSDA funding. This program includes formal coursework in the areas of scientific writing, experimental design, data interpretation, and cell biology. Research :Dr. Venkayya proposes a series of experiments to address the hypothesis that: TH2 lymphocyte product(s) can produce the biological manifestations of asthma, including airway hyperresponsiveness and mucus production, in the absence of exogenous stimuli. Airway inflammation appears to be a necessary precursor of the physiological changes seen in asthma. The mechanisms through which inflammation leads to hyperresponsiveness and mucus secretion remain to be characterized. The above hypothesis is based upon the recognition that CD4+ cells are required for the development of allergic airway inflammation and hyperresponsiveness in murine models of asthma, and that TH2 cells act as "coordinators" of this inflammation. While this role of the TH2 cell is well described, the possibility of direct "effector" function of these cells has not been explored. Dr. Venkayya's preliminary data show for the first time that TH2 lymphocyte products can directly produce airway hyperresponsiveness and mucus secretion in vivo, and mucin gene transcription in vitro. The experiments proposed by Dr. Venkayya will characterize this novel effect further and identify the lymphocyte product(s) responsible. These biological effects may result from a known lymphocyte product or a previously undescribed substance. In either case, the effects shown in the preliminary data demonstrate a new "effector" role for lymphocytes in this animal model. An understanding of the mechanism of these effects may lead to new therapies for the human disease. Environment: The Lung Biology Center and Department of Medicine are committed to the scientific and career development of Dr. Venkayya. All facilities necessary for this work are present and will be made available for his use. His advisory will continue to meet with him at six-month intervals to assess his progress. This committee is composed of five faculty members with extensive experience in the mentorship of successful scientists and in the performance of the types of studies he proposes.